Cerebellum

Meredith Phipps and Kristina Trippett


Introduction
The cerebellum, also refered to as the little brain, plays a vital role in the control of movement. It is comprised of three main lobes; vestibulocerebellum, spinocerebellum and cerebrocerebellum. The vestibulocerebellum is responsible for maintaining balance and assists in postural control. The spinocerebellum aids in error detection and modulating muscle tone, while the cerebrocerebellum is involved in action preparation and timing. The cerebellum receives input from cortical, sensory and proprioceptive areas, then projects this information to the thalamus. Damage to the cerebellum can cause significant motor impairment.

Functional Anatomy

Located posterior to the occipital lobe, the cerebellum is dorsal to the pons and medulla. The cerebellum is comprised of three main lobes; anterior, posterior and flocculonodular. The anterior and posterior lobes are divided by the primary fissure, while the posterior fissure divides the posterior and flocculondular lobes. The two longitudinal grooves divide the cerebellum into three hemispheres; vermis, intermediate and lateral.
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The outer layer, gray matter, of the cerebellum is where the processing of information takes place. White matter, the inner layer, houses the input and output fibers. The deep cerebellar nuclei, embedded in the white matter, is comprised of the dentate, interposed, fastigial nuclei. These nuclei send processed cerebellar information to other cortical and subcortical structures (4).

The three cerebellar peduncles connect the cerebellum to other parts of the nervous system. These include superior, middle, inferior peduncles. The superior peduncle, mostly efferent, has neurons located in the deep cerebellar nuclei projecting to the primary and premotor corticies. The middle peduncle, mostly afferent, has neurons in the contralateral pons which relays input from nearly all cerebral cortical areas and the superior colliculus.The middle peduncle is one of the largest pathways in the brain. The smallest pathway, the inferior peduncle, contains afferent and efferent projections. The afferent pathways bring input from the vestibular nuclei, spinal cord and brainstem while efferent pathways project to the vestibular nuclei and the reticular formation (1).
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3 Functional Regions

Vestibulocerebellum

The vestibulocerebellum, also known as the flocculonodular lobe, controls the axial muscles involved in balance and coordination of eye, body and head movements. Information from the vestibular apparatus (semicircular canals and otolithic organs) travels along cranial nerve VIII to the vestibular nuclei in the medulla directly entering into the vestbulocerebellum. Information leaving the flocculonodular lobe projects to the vestibular nuclei (acting as deep cerebellar nuclei). Information then descends on the medial and lateral vesibulospinal tracts controlling posture. Projections also ascend to aid in the vestibulo-ocular reflex. Dysfunction in this region can result in ataxic wide based gait, which is characterized by unsteady, uncoordinated walking. Other dysfunctions include postural sway and nystagmus (involuntary eye movements) (4,5).

Spinocerebellum
The spinocerebellum is in the central portions of the anterior and posterior lobes and is located in the vermis and intermediate zones. The main function is the ongoing regulation of movement via error detection. Comparing the intended action with what is actually occuring, the spinocerebellum integrates information from the motor cortex with sensory feedback. The spinocerebellum modulates muscle tone by innervating the gamma motor neurons. Somatosensory input enters the spinocerebellum through the cuneocerebellar and spinocerebellar pathways bringing proprioceptive and cutaneous information. Somatosensory inputs from the trunk and head, as well as inputs from the visual, vestibular and auditory systems enter the vermis. The intermediate zones receives projections from the distal extremeties. Outputs from the vermis exit through the fastigial nuclei descending to the briain stem and lateral vestibular nuclei. It also ascends to the thalamus and primary motor cortex. Outputs from the intermediate zone project to the interposed nuclei. Axons descend through the red nucleus to the rubrospinal tract. Ascending projections go to the thalamus and the primary and supplementary motor cortex. The spinocerebellum is somatotopically organized by functional activities, such as the hand is located near the mouth. The axial mucles are located in the vermal region and the limbs in the intermediate regions. Dysfunction in this region of the brain results in hypotonia, defined as decreased muscle tone (4,5).

Cerebrocerebellum
The cerebrocerebellum is comprised of the lateral zones of the cerebellar hemispheres. The functions include preparation of intended movement, planning and timing of voluntary movements, as well as learned and skilled movements. It also controls higher level functions of motor and nonmotor skills. Information from cortical areas are sent to the cerebrocerebellum through the pontine nuclei in the brainstem. Outputs project through the dentate nuclei to the thalamus continuing to the motor, premotor and prefrontal corticies. This information then descends in the corticospinal and reticulospinal pathways (3, 4,5).


Internal OrganizationPicture1.jpg

There are five types of neurons that process the information in the cerebellum; stellate cells, basket cells, golgi cells, purkinje cells and granule cells. The cerebellar cortex is divided intro three layers, each containing specific neurons. The outermost molecular layer houses the stellate and basket cells. It also contains granule cell axons as well as purkinje and golgi cell dendrites. The purkinje layer, the middle layer, is comprised of a single layer of purkinje cell bodies. The granule cells are located deep in the cortex in the granule cell layer.

The cells that assit with cerebellar processing are basket, stellate and golgi cells. Basket cells work by inhibiting the purkinje cells bodies while the stellate cells inhibit the purkinje cell dendrites. These both receive input from parallel fibers, inhibiting the surrounding purkinje cells, that localize the signal. The golgi cells work in a similar fashion by inhibiting the granule cells.

Input
Information from the spinal cord, cortical and subcortical brain structures enter into the cerebellum via two types of afferent fibers: mossy and climbing fibers. Mossy fibers, the main afferent fibers entering the cerebellum, orginate in the spinal cord, pontine, vestibular and reticular nuclei, and somatosensory receptors. These have an excitatory synapse with the granule cells, but do not directly synapse with the purkinje cells. Each granule cell receives input from multiple mossy fibers, and each mossy fiber influences several granule cells. The granule cell axons ascend into the molecular layer where it bifurcates, forming the parallel fibers. These fibers then transmit the signal to the purkinje cell dendrites. Unlike the mossy fibers, climbing fibers bring input exclusively from the contralateral inferior olive in the medulla. The olive receives information from the spinal cord, cortical and subcortical structures. Climbing fibers synapse directly with purkinje fibers by wrapping around them producing a strong excitatory synapse (1, 4).


Output
Most output from the cerebellum goes through the deep cerebellar nuclei. The purkinje cells are GABAergic and therefore have an inhibitory effect on the deep cerebellar nuclei. The climbing and mossy fibers have a direct excitatory connection with the deep cerebellar nuclei. The complex cerebellar connections can be better understood by looking at the figure below which explains the process as a deep excitatory loop and cortical inhibitory loop. The deep excitatory loop consists of the excitatory connections of the mossy and climbing fibers on the deep cerebellar nuclei. The cortical inhibitory loop shows the purkinje cells' inhibitory effect on the deep cerebellar nuclei. The information is then transmitted to the thalamus and continues on to wherever it is needed (4,5).

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Main Functions in Control of Movement


Error Detection
The cerebellum detects errors in movement by comparing what is actually occuring to the intended action. Information from the motor cortex is sent to the spinal cord which produces movement. An efferent copy is also sent to the cerebellum. Somatosensory, auditory and visual inputs provide information about this movement to the cerebellum enabling evaluation of the action. The result is then projected to the thalamus and red nucleus continuing to the corticies (4).

Coordination and Timing of Movement
Working with the basal ganglia and the motor corticies, the cerebellum plays an active role in coordination and the timing of movement. The role of the cerebellum in this process is to integrate sensory information with learned information (2,7). On top of this, the cerebellum is responsible for rhythmic movements, such as walking, writing and scratching. The cerebellum is able to make adjustments in the timing of these movements and facilitates the action.

Postural Control
The cerebellum is responsible for maintaining upright posture during movement through inputs from the vestibular apparatus and proprioceptive inputs.

Other Functions
The other functions of the cerebellum include modulating muscle tone, motor learning, cognitive functions, control of emotions and other nonmotor functions (4,6).


General Dysfunctions
Damage to the cerebellum can result in a number of motor deficts. Ataxia, a condition that involves lack of coordination between movements of body parts, is one of these deficits. The term is often used in reference to gait or movements of a specific body part. Another cerebellar condition is known as dysmetria, which is the inability to make a movement in the direction or distance that is desired. Two types of dysmetria are hypometria, undershooting a target, and hypermetria, overshooting a target (3). Abnormal agonist-antagonist control is a result of dysdiadochokinsia which is the inability to make rapid, alternating movements of a limb. Another deficit that can occur in the cerebellum is asynergia which is the impairment of cooridination, making it difficult for the person to manage multilimb movements. Damage to the spinocerebellum could result in hypotonia, decreased muscle tone. An example of this is arms swinging freely and the appearance of looking 'floppy'. Nystagmus, involunatry eye movements, is another dysfunction of the cerebellum. The final main cerebellar deficit is an action or intention tremor. This is characterized by involunatry oscilation, or shaking, of the limb during movement, but is absent when the limb is at rest. Other deficits that may occur could impair planing and timing of movement, or in motor learning (4,5).







Conclusion
The cerebellum, located posterior to the occipital lobe, is comprised of three functional regions that aid in the control of movement. The functions of the cerebellum include error detection,postural control, coordination and timing of movement, as well as other nonmotor functions. This structure is vital to any functional movement and is therefore very important.

Glossary
Ataxic gait: A disorder in the cerebellum that involves lack of coordination between movements of body parts

Basket Cells: Inhibitory interneurons in the cerebellar cortex whose cell bodies are located within the Purkinje cell layer and whose axons make basketlike terminal arbors around Purkinje cell bodies

Cerebellar Peduncles: The three bilateral pairs of axon tracts (inferior, middle, and superior cerebellar peduncles) that carry information to and from the cerebellum

Cerebrocerebellum: The part of the cerebellar cortex that receives input from the cerebral cortex via axons from the pontine relay nuclei

Climbing Fibers: Axons that orginate in the inferior olive, ascend through the inferior cerebellar peduncle, and make terminal arborizations that invest the dendritic tree of Purkinje cells

Deep Cerebellar Nuclei: The nuclei at the base of the cerebellum that relay information from the cerebellar cortex to the thalamus. Includes dentate, fastigial and interpose nuclei

Dysdiadochokinsia: A cerebellar dysfunction characterized by the inability to make rapid alternatin movements of the limb

Dysmetria: Cerebellar dysfunction characterized by an inability to make a movement in the appropriate direction or at the suitable distance

Golgi Cell: Located in the granule cell layer and provides inhibitory feedback to the granule cells

Granule Cell: Located in the granule cell layer and receives input from mossy fibers projecting to parallel fibers

Gray matter: General term that describes regions of the central nervous system rich in neuronal cell bodies and neurophil; includes the cerebral and cerebellar corticies, the nuclei of the brain, and the central portion of the spinal cord

Hypotonia: Decrease in muscle tone

Inferior Olive: (inferior olivary nucleus) Prominent nucleus in the medulla; a major source of input to the cerebellum

Mossy Fibers: Axons from the pontine nuclei that bring information into the cerebellum

Motor Cortex: The region of the cerebral cortex lying anterior to the central sulcus concerned with motor behavior; includes the primary motor cortex in the precentral gyrus and associated cortical areas in the frontal lobe

Nystagmus: Leterally, a nodding movement. Refers to repetitive movements of the eyes normally elicited by large-scale movements of the visual field (otokinetic nystagmus). Nystagmus in the absence of appropriate stimuli usually indicates brainstem or cerebellar pathology

Pontine Nuclei: Located in the pons, a component of the brainstem

Posterior Fissure: Divides the posterior and flocculonodular lobe of the cerebellum

Primary Fissure: Divides the anterior and posterior lobes of the cerebellum

Purkinje Cell: Large principal projection neuron of the cerebellar cortex

Somatosensory Cortex: Region of the cerebral cortex concerned with processing sensory information from the somatosensory receptors

Spinocerebellum: Region of the cerebellar cortex that receives input from the spinal cord

Stellate Cell: Located in the molecular, it inhibits the purkinje cell dendrites

Thalamus: Collection of nuclei that relays sensory information from lower centers to the cerebral cortex

Vestibulocerebellum: Part of the cerebellar cortex that receives direct input from the vestibular nuclei

Vestibulo-ocular reflex: Involuntary movement of the eyes in response to head movement. Retinal images remain stable while the head is moving

White Matter: General term that refers to large axon tracts in the brain and spinal cord


Quiz Questions
Multiple Choice

1) Which lobe modulates muscle tone?
a. Vestibulocerebellum
b. Cerebrocerebellum
c. Spinocerebellum
d. A and C
e. A and B
f. B and C
g. All of the above
h. None of the above

2) Which cells are directly involved in cerebellar processing?
a. Climbing fibers
b. Basket cells
c. Golgi cells
d. Purkinje cells
e. Granule Cells
f. Stellate Cells
g. Mossy Fibers
h. A, B ,C
i, D, E, F, G
j. D and E
k. A and C
l. F and G
m. All of the above
n. None of the above

3) What is dysdiadochokinsia?
a. Lack of coordination between movements of body parts
b. The inability to make rapid alternating movements of a limb
c. Undershooting a target
d. Overshooting a target
e. Inability to manage multilimb movements
f. B and E
g. C and D

4) The following are functions of the cerebellum EXCEPT...
a. Error Detection
b. Postural Control
c. Initiation of movement
d. Coordinating Timing and Movement
e. Muscle Tone
f. Control of emotions
g. All of the above ARE functions of the cerebellum

5) The cerebellum is located
a. Posterior to the occipital lobe
b. Dorsal to the pons and the medulla
c. Anterior to the occipital lobe
d. Ventral to the pons and medulla
e. A and B
f. C and D
g. A and D
h. B and C

True / False
6) All cerebellar outputs go through the deep cerebellar nuclei.
7) The mossy fibers synapse with the granule cells, purkinje cells and deep cerebellar nuclei
8) The purkinje layer is located in the middle of the cerebellar cortex.
9) The cerebrocerebellum is in the lateral zones of the cerebellar hemisphere.
10) Outputs from the intermediate zone project to the fastigial deep cerebellar nuclei.

Short Answer
11) Diagram the mossy and climbing fiber loops
12) Name the three functional regions of the cerebellum and list their functions.
13) Name and clasify 4 dysfunctions that can occur in the cerebellum


Answers
1) C
2) J
3) B
4) C
5) E
6) False- The output of the vestibulocerebellum do not go through the deep cerebellar nuclei
7) False- Not with purkinje cells
8) True
9) True
10) False, Outputs from the intermediate zone project to the interpose deep cerebellar nuclei

Suggested Readings

References
  1. Gray, E. G. "The Granule Cells, Mossy Synapses, and Purkinje Spine Synapses of the Cerebellum." Journal of Anatomy 95.3 (1961): 345-356. Web. http://ncbi.nlm.gov/pmc/articles/PMC1244490/
  2. Mauk. M. D., J. F. Medina, W. L. Nores, and T. Ohyama. "Cerebellar Function: Coordination, Learning or Timing." Current Biology 10.14 (2000): 522-25. Web. http://www.cell.com/current-biology/retrieve/pii/S09609822000005844
  3. O'Reilly, Jill X., M. Marsel Mesulam, and Anna Christina Nobre. "The Cerebellum Predicts the Timing of Perceptual Events." The Journal of Neuroscience 28.9 (2008): 2252-2260. Web. http://www.jneurosci.org/cgi/content/short/28/9/2253
  4. Purves, Dale. Neuroscience. Sutherland, Mass.: Sinauer, 2008. Print
  5. Squire, Lary R. Fundamental Neuroscience. Amsterdam: Academic, 2003, Print
  6. Rapoport, Mark, Robert Van Reekum, and Helen Mayberg. "The Role of the Cerebellum in Cognition and Behavior." Journal of Neuropsychiatry Clin Neurosci 12 (2000): 193-198. Web. http://neuro.psychiatryonline.org/cgi/content/abstract/12/2/193
  7. Tharch, W. T., H.P Goodkin, and J. G. Keating. "The Cerebellum and the Adaptive Coordination of Movement." Annual Review of Neuroscience 15 (1992): 403-442. Web. http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.ne.15.030193.002155.